The Systems Biochemistry of Adaptation in Cellular Protein Networks. A living cell must process and interpret a host of diverse signals using a complex network of interacting proteins inside the cell. The detailed molecular mechanisms by which cells exhibit adaptation to these signals remains a fundamental question in biology. This project aims to develop a novel mathematical framework for analysing the capacity of intracellular protein interactions to contribute to cellular adaptation, along ....The Systems Biochemistry of Adaptation in Cellular Protein Networks. A living cell must process and interpret a host of diverse signals using a complex network of interacting proteins inside the cell. The detailed molecular mechanisms by which cells exhibit adaptation to these signals remains a fundamental question in biology. This project aims to develop a novel mathematical framework for analysing the capacity of intracellular protein interactions to contribute to cellular adaptation, along with a novel methodology for validating mathematical models against experimental data. These innovations offer a completely fresh approach to identifying and modulating the adaptive capacities of living cells, which may contribute to overcoming the problem of drug resistance in future therapeutic development.
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Discovery Early Career Researcher Award - Grant ID: DE130101191
Funder
Australian Research Council
Funding Amount
$375,000.00
Summary
Formation of the osteocyte network in bone matrix. The formation of new bone, which occurs throughout life for bone renewal and acutely after fractures, entraps a network of cells that can detect micro-damage and direct repair mechanisms. Mathematical and computational methods will be used to understand how this network can lead to a self-detecting and self-repairing biomaterial.
Dynamics of atherosclerotic plaque formation, growth and regression. This project aims to provide a mathematical framework to interpret plaque growth. Many biological processes contribute to the growth of atherosclerotic plaques inside arteries. Lipoproteins enter the artery walls and stimulate tissues to signal to cells which duly respond so that fatty streaks form and grow into dangerous plaques that cause heart attacks or stroke. These processes are often nonlinear and operate on widely varyi ....Dynamics of atherosclerotic plaque formation, growth and regression. This project aims to provide a mathematical framework to interpret plaque growth. Many biological processes contribute to the growth of atherosclerotic plaques inside arteries. Lipoproteins enter the artery walls and stimulate tissues to signal to cells which duly respond so that fatty streaks form and grow into dangerous plaques that cause heart attacks or stroke. These processes are often nonlinear and operate on widely varying time scales. The project plans to use systems of ordinary differential equations, partial differential equations with non-standard boundary conditions, and bifurcation theory to find how nonlinear processes shape plaque growth. The expected results may demonstrate the importance of bifurcations, dynamics and nonlinear systems in plaque growth and provide new models to interpret biological data.Read moreRead less
Understanding the robustness and plasticity of metabolite concentrations. This project aims to further the understanding of how organisms mitigate the effects of changing environment by altering metabolite concentrations, important for food quality, energetics, and health. Through this understanding, the project provides the potential to precisely tailor metabolic intervention strategies, highly beneficial for applied sciences. The expected outcome of the project is a suite of computational appr ....Understanding the robustness and plasticity of metabolite concentrations. This project aims to further the understanding of how organisms mitigate the effects of changing environment by altering metabolite concentrations, important for food quality, energetics, and health. Through this understanding, the project provides the potential to precisely tailor metabolic intervention strategies, highly beneficial for applied sciences. The expected outcome of the project is a suite of computational approaches that allow for integration of large-scale data with networks to predict metabolite concentration ranges. This will provide significant benefit with the aim of maintaining outstanding research in Australia, and has clear potential for improved human health and enhanced food quality via metabolic reprogramming.Read moreRead less
Stochastic modelling of telomere length regulation in ageing research. This project will design innovative stochastic models to explore the molecular mechanisms governing telomere length regulation and their critical roles in determining cell fate. Computer simulations will provide testable predictions regarding the crucial functions of noise in generating the heterogeneity of telomere length.
System identification of microstructure in the brain using magnetic resonance. Magnetic Resonance Imaging technologies will be exploited to probe the microstructure of the brain, using powerful Bayesian optimisation techniques and innovative uses of magnetic resonance. The project will in particular develop non-invasive imaging methods to quantify iron content in the brain, important for research on dementia and Alzheimer's disease.
Complex dynamical systems: inferring form and function of interacting biological systems. Often in biology a large number of simple parts interacting according to simple rules can result in behaviour that is rich and varied. This project aims to develop the mathematics of complex systems theory to describe how such collections of simple interacting parts can form large complicated structures, and to deduce what dynamical behaviour can result.
Systems modelling of the cardiac fibroblast. The cardiac fibroblast is a specialised cell in the heart. New evidence shows that this cell type is central to heart function, but relatively little is known about how and why. This project will develop mathematical modelling to characterise how the cardiac fibroblast regulates the functioning of the adult heart.
Phylodynamics for Single Cell Genomics . This project generates the mathematical framework required to look at single cell data in developmental systems and tissues. All cells in a multi-cellular organism derive from a single ancestral cell, generally the fertilised egg cell. Phylodynamics provides a framework to analyse and model this data, by connecting the shared ancestry of cells in an organism to the cell population and tissue dynamics. By developing the mathematical and statistical foundat ....Phylodynamics for Single Cell Genomics . This project generates the mathematical framework required to look at single cell data in developmental systems and tissues. All cells in a multi-cellular organism derive from a single ancestral cell, generally the fertilised egg cell. Phylodynamics provides a framework to analyse and model this data, by connecting the shared ancestry of cells in an organism to the cell population and tissue dynamics. By developing the mathematical and statistical foundations for the analysis of single cell data in a phylodynamic framework we will establish a powerful new computational tools for the analysis of tissues and developmental processes. Read moreRead less
Mathematical Modelling of the Mechanobiology of Arterial Plaque Growth. Plaque growth is a chronic inflammatory response induced by the interactions between endothelial cells, lipids, monocytes/macrophages, smooth muscle cells and platelets in the arteries. It involves many different biological processes, such as lipid deposition, inflammation and angiogenesis, and their interactions with the microcirculation. To understand the underlying mechanobiology, we propose to develop a mathematical mode ....Mathematical Modelling of the Mechanobiology of Arterial Plaque Growth. Plaque growth is a chronic inflammatory response induced by the interactions between endothelial cells, lipids, monocytes/macrophages, smooth muscle cells and platelets in the arteries. It involves many different biological processes, such as lipid deposition, inflammation and angiogenesis, and their interactions with the microcirculation. To understand the underlying mechanobiology, we propose to develop a mathematical model to interpret plaque growth by integrating these dynamic biological processes. It will offer a systematic rational understanding of plaque growth. New models will be provided to better interpret biological data and contribute to our knowledge in quantifying complex biological mechanisms during growth and development.Read moreRead less